Assessment of Binding Site and Development of Small Molecule Inhibitors Targeting Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer (NSCLC)

被引：4

作者：

Karnik, Kshipra S. ^{[1
]}

Sarkate, Aniket P. ^{[1
]}

Rajhans, Aishwarya P. ^{[1
]}

Wakte, Pravin S. ^{[1
]}

机构：

[1] Dr Babasaheb Ambedkar Marathwada Univ, Dept Chem Technol, Aurangabad 431004, India

来源：

LETTERS IN DRUG DESIGN & DISCOVERY | 2023年 / 20卷 / 09期

关键词：

Non-small cell lung cancer; EGFR; library design; virtual screening; molecular docking; molecular dynamics simulations; TYROSINE KINASE INHIBITORS; PYRIMIDINE-DERIVATIVES; SOMATIC MUTATIONS; EGFR; DOCKING; ANTICANCER; PYRAZOLE; CONFORMATION; MECHANISMS; SIMULATION;

D O I：

10.2174/1570180819666220523150059

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Background Mutations occurring in the epidermal growth factor receptor of the tyrosine kinase family concerned with non-small cell lung cancer have been specifically targeted. Objectives The library design and R-group enhancement technique have been carried out on the pre-existing marketed drugs to increase the binding affinity of the designed novel compounds. The screening of compounds was done using a flexible docking protocol. Methods Molecular docking studies provided information about binding pockets and interactions of molecules with the mutant (PDB: 4I1Z) as well as wild-type (PDB: 4I23) EGFR enzymes. The flexible docking was well supported by ADMET and molecular dynamic simulation studies. Results On the basis of docking score and protein-ligand interactions, the highest-scoring molecule was selected for molecular dynamics simulation, providing a complete insight into the ligand interaction and saturation. Conclusion The screened molecules can act as potential EGFR inhibitors in the management of drug resistance.

引用

页码：1204 / 1218

页数：15

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